Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical studies were performed to clarify the significance of the expression or overexpression of epidermal growth factor (EGF), EGF-receptor (EGFR), p53, v-erb B, ras p21 in 23 cases each of tubular adenoma and adenocarcinoma. The expression of EGF, EGFR, p53, v-erb B, and ras p21 in paraffin-embedded tissues, from 46 patients with colorectal tumors (adenoma: 23 cases; 14 mild dysplasia, six moderate dysplasia, three severe dysplasia, adenocarcinoma: 23 cases; 17 well differentiated, two moderately differentiated, three poorly differentiated, one mucinous carcinoma was analyzed immunohistochemically using anti-EGF, EGFR, p53, v-erb B and ras p21 antibodies. The EGF and ras p21 tended to express more strongly in carcinoma cases than in the adenoma cases, and in severe and moderate dysplasia than in mild dysplasia (EGF: stained positive in five adenomas [21.74%] and 17 adenocarcinomas [73.91%]; ras p21: stained positive in six adenomas [26.09%] and 14 adenocarcinomas [60.87%]. The EGFR stained positive in two adenomas (8.70%) and two adenocarcinomas (8.70%). The p53 and v-erb B showed positive staining only in the carcinoma cases (p53: stained positive in four cases [17.39%]; v-erb B: stained positive in eight cases [34.78%]). This study suggests that these factors seem to have some role in the progression of colon neoplasms. It suggests that genetic alteration is not always equal to the overexpression of protein products, but that it reflects them well, and that the staining makes some contribution to differential diagnosis in colorectal neoplasms.
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PMID:Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues. 791 78

The p53-inducible gene WAF1/CIP1 encodes a M(r) 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G1 arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 "knock-out" mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by gamma-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed.
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PMID:Induction of WAF1/CIP1 by a p53-independent pathway. 801 56

We recently described culture conditions that allow proliferation of metastatic human breast cancer cells from biopsy specimens of certain patient samples. These conditions resulted in the development of an immortalized cell strain designated SUM-44PE. These same culture conditions were used to isolate a human breast cancer cell strain from a metastatic lymph node of a separate breast cancer patient. The SUM-16LN human breast cancer cells isolated from this specimen were cultured either in serum-free medium or serum-containing medium supplemented with insulin and hydrocortisone. Unlike the SUM-44PE cells that have proliferated in culture continuously for over two years, SUM-16LN cells proliferated in culture for approximately 200 days and underwent 15 to 20 population doublings before undergoing cell senescence. No cells of this strain proliferated beyond passage 8. SUM-16LN cells were keratin-19 positive and had an aneuploid karyotype. These cells overexpressed p53 protein and had an amplified epidermal growth factor (EGF) receptor gene that resulted in high level expression of tyrosine phosphorylated EGF receptor protein. Despite the presence of high levels of tyrosine phosphorylated EGF receptor in these cells, they proliferated in serum-free, EGF-free medium and did not secrete detectable levels of EGF-like mitogenic growth factor. In addition, these cells were potently growth inhibited by all concentrations of exogenous EGF tested and by the neutralizing EGF receptor antibody Mab 425. These results suggest that the high level of tyrosine phosphorylated EGF receptor present in these cells is the direct result of receptor overexpression and not the result of the presence of a stimulatory ligand. Thus, SUM-16LN represents a human breast cancer cell strain that exhibited genetic and cellular characteristics of advanced human breast cancer cells. Nevertheless, these cells exhibited a finite proliferative lifespan in culture, suggesting that cellular immortalization is not a phenotype expressed by all human breast cancer cells.
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PMID:Finite proliferative lifespan in vitro of a human breast cancer cell strain isolated from a metastatic lymph node. 801 55

Three stable carcinoma cell lines, designated RM22-F5, RM17-5R, and RM1-4, were established from spontaneously occurring mammary carcinomas in old, outbred, female Wistar rats. The RM22-F5 and RM17-5R cells were keratin-positive and formed epithelial monolayers, whereas RM1-4 cells exhibited a spindle-like morphology and intense vimentin staining. When injected into nude mice, RM22-F5, RM17-5R and RM1-4 cells formed well-differentiated, poorly differentiated and undifferentiated carcinomas, respectively. The relative growth rates of the tumor cells in vitro were RM1-4 > RM22-F5 > RM17-5R. The growth of RM22-F5, but not of RM17-5R and RM1-4 cells, was significantly stimulated by insulin, epidermal growth factor, dexamethasone, 17 beta-estradiol and progesterone in vitro. Ovariectomy reduced the growth of RM22-F5 cells in vivo and these cells (but not RM1-4 or RM17-5R) were estrogen-receptor (ER)-positive. None of the lines were positive for the progesterone receptor (PR). Spontaneous lung and lymph-node metastases were observed in nude mice injected with RM22-F5 or RM17-5R cells, respectively. In contrast, RM1-4 cells were non-metastatic but invasive. Karyotype analysis revealed that RM22-F5 cells were hyperdiploid, RM17-5R were hypotetraploid, and RM1-4 were diploid with a sizeable insertion in chromosome 1. A point mutation in codon 12 (G to A transition) and loss of the normal allele of the H-ras-1 gene was detected in the DNA from RM22-F5 cells. No p53 mutations were apparent in any of the cell lines. The results indicate that RM22-F5 cells are hormone-dependent with an ER+/PR- phenotype, while the RM17-5R and RM1-4 lines are hormone-independent and ER-/PR-. These cell lines exhibit the spectrum of biological properties and genetic alterations observed in human breast cancers and may, therefore, be novel and useful models for understanding sporadic breast cancer in post-menopausal women.
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PMID:Establishment of hormone-dependent and hormone-independent carcinoma cell lines with different metastatic potentials from spontaneous mammary tumors in aged Wistar rats. 805 57

Calcium enhances keratinocyte differentiation, and 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is both antiproliferative and prodifferentiative in many cell types, including normal human keratinocytes. In the present study, we examined the combined effects of calcium and 1,25(OH)2D3 on parameters of growth and differentiation and on c-fos and p53 gene expression in normal human keratinocytes. Exposure of normal human keratinocytes to 1,25(OH)2D3 markedly reduced [3H] thymidine incorporation and cell number at low and high medium Ca++ concentrations. Simultaneously, cells in the G0/G1 phase of the cell cycle increased significantly and those in the S phase fell precipitously. 1,25(OH)2D3 and calcium also induced keratinocyte differentiation independently, as assessed by immunocytochemistry and by induction of involucrin mRNA. Both Ca++ and 1,25(OH)2D3 were shown, by nuclear run-on assays, to increase involucrin gene transcription. A rapid, transient elevation in c-fos protooncogene expression preceded these effects when epidermal growth factor was present alone. When 1,25(OH)2D3 was added to quiescent keratinocytes, there was a marked augmentation of c-fos mRNA accumulation at low and high medium Ca++ concentrations. Varying medium Ca++ concentrations had no effect on c-fos mRNA levels. Increasing medium Ca++ concentrations from 0.15 to 2.0 mM produced marked elevations of p53 mRNA accumulation and of the rate of p53 gene transcription, whereas 1,25(OH)2D3 had no effect. These results, therefore, suggest that 1,25(OH)2D3 and calcium act in concert to modulate the expression of two important cell-cycle-associated genes, which may be important components in the initial programming of growth and differentiation of normal human keratinocytes.
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PMID:Effect of 1,25 dihydroxyvitamin D3 and calcium on growth and differentiation and on c-fos and p53 gene expression in normal human keratinocytes. 807 97

Amphiregulin is a recently described member of the epidermal growth factor family. Primary breast cancers were assessed for expression of amphiregulin by immunochemistry (111 cases), Northern, and/or dot blots (68 cases). Epidermal growth factor and estrogen receptors were measured in all cases. p53 and erbB-2 expression was assessed by immunohistochemistry for most cases. There was no association of these factors with amphiregulin expression, which was detected by immunochemistry in 40 of 111 cases. A significant association of amphiregulin expression assessed by Northern dot blots versus immunochemical staining was seen (P = 0.0016). Expression was not detected in adjacent nontumor tissue by immunochemistry. Amphiregulin was expressed in tumor epithelium, but not stromal or inflammatory cells. Expression was more common in lymph node positive cases (23 of 49; 47%) than lymph node negative cases (11 of 42; 26%; P = 0.04). The coexpression of epidermal growth factor receptor and amphiregulin in 35% of epidermal growth factor receptor positive cases raises the possibility of an autocrine loop in this subset of patients. Amphiregulin stimulates fibroblast growth and is up-regulated in breast cancer. A possible effect on tumor stroma may relate to the association with metastases.
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PMID:Amphiregulin, epidermal growth factor receptor, and estrogen receptor expression in human primary breast cancer. 810 63

Recent evidence suggests that wild-type p53 prevents cell-cycle progression after DNA damage, which may provide a sufficient period for the cells to repair the genetic lesions that may otherwise lead to cell death or cellular transformation. We tested whether this hypothesis is generally applicable to parenchymal cells of internal organs. When primary neonatal rat hepatocytes were exposed to a nonlethal dose of ultraviolet light, actinomycin D, or mitomycin C, most cells expressed abundant p53 with an abnormally extended half life in their nuclei, and their growth was arrested despite treatment with growth factors (epidermal growth factor and insulin). When DNA-damaged cells were treated with p53-antisense oligonucleotides, p53 expression was significantly suppressed, and an appreciable fraction of the cells entered S phase. However, when damaged cells were administered p53-sense or retinoblastoma susceptibility gene-antisense oligonucleotides, there was no recovery from growth arrest. The data strongly suggest that p53 is a component of at least one signal transduction pathway leading to growth arrest in DNA-damaged cells.
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PMID:Recovery from ultraviolet-induced growth arrest of primary rat hepatocytes by p53 antisense oligonucleotide treatment. 814 18

The effects of the bioflavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) on the growth and cell cycle progression of the human breast cancer cell line MDA-MB468 have been studied. Quercetin inhibited cell proliferation with an IC50 (a drug concentration which inhibited growth by 50% following a 3-day exposure) value of 7 micrograms/ml. In actively growing cultures, the addition of quercetin resulted in the accumulation of cells at the G2-M phase. We have correlated these effects on cell proliferation with the observation that quercetin strongly inhibited, in a time- and dose-dependent fashion, the expression of the mutated p53 protein, which is the only form present at high levels in this cell line. This inhibition takes place at the translational level. Quercetin did not affect the steady-state mRNA levels of p53, but prevented the accumulation of newly synthesized p53 protein. This quercetin action appeared to be somewhat specific for p53 because the drug did not alter the amount of other proteins present in MDA-MB468 cells such as P-glycoprotein and did not prevent the induction of the synthesis of epidermal growth factor receptor in response to epidermal growth factor.
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PMID:Quercetin mediates the down-regulation of mutant p53 in the human breast cancer cell line MDA-MB468. 816 91

The expression of three epidermal growth factor (EGF)-related peptides, transforming growth factor alpha (TGF-alpha), amphiregulin (AR) and cripto-1 (CR-1), was examined by immunocytochemistry (ICC) in 68 primary infiltrating ductal (IDCs) and infiltrating lobular breast carcinomas (ILCs), and in 23 adjacent non-involved human mammary tissue samples. Within the 68 IDC and ILC specimens, 54 (79%) expressed immunoreactive TGF-alpha, 52 (77%) expressed AR and 56 (82%) expressed CR-1. Cytoplasmic staining was observed with all of the antibodies, and this staining could be eliminated by preabsorption of the antibodies with the appropriate peptide immunogen. Cytoplasmic staining with all of the antibodies was confined to the carcinoma cells, since no specific immunoreactivity could be detected in the surrounding stromal or endothelial cells. In addition to cytoplasmic reactivity, the AR antibody also exhibited nuclear staining in a number of the carcinoma specimens. No significant correlations were found between the percentage of carcinoma cells that were positive for TGF-alpha, AR or CR-1 and oestrogen receptor status, axillary lymph node involvement, histological grade, tumour size, proliferative index, loss of heterozygosity on chromosome 17p or overall patient survival. However, a highly significant inverse correlation was observed between the average percentage of carcinoma cells that expressed AR in individual tumours and the presence of a point-mutated p53 gene. Likewise, a significantly higher percentage of tumour cells in the ILC group expressed AR as compared with the average percentage of tumour cells that expressed AR in the IDC group. Of the 23 adjacent, non-involved breast tissue samples, CR-1 could be detected by ICC in only three (13%), while TGF-alpha was found in six (26%) and AR in ten (43%) of the non-involved breast tissues. These data demonstrate that breast carcinomas express multiple EGF-related peptides and show that the differential expression of CR-1 in malignant breast epithelial cells may serve as a potential tumour marker for breast cancer.
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PMID:Expression of transforming growth factor alpha, amphiregulin and cripto-1 in human breast carcinomas. 818 21

Human squamous carcinoma A431 cells express a high level of epidermal growth factor (EGF) receptor. The cells carry only a mutated form of the p53 gene, the G-->A mutation at codon 273 which results in an arginine to histidine substitution (mp53). The temporal changes of EGF receptor, c-Raf-1, mp53, and cell cycle distribution in A431 cells after 1-h exposure to doxorubicin (DOX) are examined. EGF receptor in A431 cells is inactivated at 5 min; subsequently, the receptor level increases and reaches its maximum 4-8 h after DOX treatment. Dephosphorylation of c-Raf-1 is detected at 30 min and the decay of the protein is demonstrated at 8 h in cells after exposure to DOX. The level of mp53 in A431 cells remains unchanged for 8 h after DOX treatment but increases by about 20-fold at 24 h. There is no significant change in cell cycle distribution in A431 cells for up to 8 h after DOX exposure, whereas cells are accumulated in S and G2-M phases by 24 h. It is postulated that DOX inactivates EGF signal transduction and induces mp53. The increase in mp53 is coincident with DOX-induced G2-M block in cells.
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PMID:Up-regulation of a mutant form of p53 by doxorubicin in human squamous carcinoma cells. 818 62


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